Portal hypertension is defined as an increase in the pressure gradient between the portal vein and hepatic veins or the inferior vena cava (IVC). Common complications of portal hypertension include gastroesophageal varices, ascites, and portasystemic encephalopathy. Patients with cirrhosis have a 5-10% yearly incidence of variceal formation, and a 4-15% yearly incidence of bleeding. Each bleeding episode carries up to a 20% risk of death. Consequently, the development of an accurate noninvasive technique for measurement of portal venous pressure would represent a major advance in the diagnosis and management of portal hypertension. Our group has proposed and patented a novel and innovative ultrasound technique called subharmonic-aided pressure estimation (SHAPE) for noninvasive pressure measurements and this application brings together basic scientists (who developed the fundamental concept of SHAPE) and clinicians from Thomas Jefferson University (TJU) with a premier manufacturer of ultrasound scanners (GE Healthcare) in order to produce a device for noninvasive and accurate assessment of portal hypertension. The SHAPE algorithm will be implemented on a state-of-the-art ultrasound scanner (Logiq 9, GE Healthcare, Milwaukee, WI) for real time pressure measurements. The in vivo SHAPE results will be calibrated based on manometer-tipped catheter (i.e., pressure transducer) measurements in the IVC, hepatic and portal veins of 5 canines. Finally, the novel implementation of SHAPE will be tested in 45 patients undergoing a trans-jugular liver biopsy at TJU. In all cases hepatic venous pressures will be measured and Child Pugh as well as MELD scores calculated. Corresponding SHAPE measurements will be performed and the results compared to the clinical data. In conclusion, this proposal aims to develop a novel and innovative ultrasound based method (i.e., SHAPE) for noninvasive and accurate evaluation of portal hypertension in vivo and to translate this technology from pre-clinical studies to application in patients. PUBLIC HEALTH RELEVANCE: Increased pressure in the blood vessels of the liver, especially the portal vein, can lead to significant complications including internal bleeding. Each bleeding episode carries up to a 20% risk of death. An accurate marker for portal hypertension would impact literally millions of Americans with liver disease. This project will bring together basic scientists and clinicians from Thomas Jefferson University with a premier manufacturer of ultrasound scanners (GE Healthcare) in order to produce a device for noninvasive and accurate assessment of portal pressures.